Search results for "Cancer vaccine"

Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector-based vaccination in mice, but not man.

2002

Mutations and aberrant expression of the p53 tumor suppressor protein are the most frequent molecular alterations in human malignancy. Peptides derived from the wild-type (wt) p53 protein and presented by major histocompatibility complex (MHC) molecules for T lymphocyte recognition are believed to serve as universal tumor-associated antigens for cancer immunotherapy. We studied the immunogeneicity of a recombinant replication-defective adenoviral vector encoding human full-length wt p53 (rAd/hup53) in human leukocyte antigen (HLA)-A2K(b)-transgenic (Tg) mice and man. The generation of p53 epitope-specific cytotoxic T lymphocytes (CTLs) in p53-proficient and p53-deficient A2K(b)-Tg mice was …

More about genetically modified tumour vaccines

1998

Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: impact of the cluster effect on the killing of tumor cells.

2014

Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor-associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl-TN antigen showed a significant cluster effect. It induced in mice prevailing IgG2a antibodies, which bind to MCF-7 breast tumor cells and initiate the killing of these tumor cells by activation of the complement-dependent cytotoxicity complex.

CpG-Loaded Multifunctional Cationic Nanohydrogel Particles as Self-Adjuvanting Glycopeptide Antitumor Vaccines

2014

Self-adjuvanting antitumor vaccines by multifunctional cationic nanohydrogels loaded with CpG. A conjugate consisting of tumor-associated MUC1-glycopeptide B-cell epitope and tetanus toxin T-cell epitope P2 is linked to cationic nanogels. Oligonucleotide CpG complexation enhances toll-like receptor (TLR) stimulated T-cell proliferation and rapid immune activation. This co-delivery promotes induction of specific MUC1-antibodies binding to human breast tumor cells without external adjuvant.

An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors.

2019

A one-two, CAR-T cell punch Chimeric antigen receptor (CAR)–T cells have been clinically effective in killing certain hematological malignancies, but achieving long-term patient responses for solid tumors remains a challenge. Reinhard et al. describe a two-part “CARVac” strategy to overcome poor CAR-T cell stimulation and responses in vivo. They introduce the tight junction protein claudin 6 (CLDN6) as a new CAR-T cell target and designed a nanoparticulate RNA vaccine encoding a chimeric receptor directed toward CLDN6. This lipoplex RNA vaccine promotes CLDN6 expression on the surface of dendritic cells, which in turn stimulates and enhances the efficacy of CLDN6-CAR-T cells for improved tu…

Harnessing dendritic cells in cancer.

2011

Dendritic cells (DCs) are central to the initiation of tumor-specific immune responses. However, the tumor microenvironment generates immunosuppressive cells and soluble mediators that compromise DC functions and limit the success of DC-based therapies. Progress in understanding DC metabolism in cancer is uncovering novel therapeutic targets that could restore DC capacity to prime T cells and trigger effective anticancer responses. Accumulating evidence also indicates that conventional chemo- and radiotherapy protocols can cause DC activation, enhance antigen cross-presentation, selectively eliminate immunosuppressive cells and revert the immunosuppression state caused by cancer, suggesting…

Antitumor Cell-Complex Vaccines Employing Genetically Modified Tumor Cells and Fibroblasts

2014

The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok) and a low producer (p2F). Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP) IgG. In the g…

Dexamethasone premedication suppresses vaccine-induced immune responses against cancer

2020

ABSTRACT Glucocorticosteroids (GCS) have an established role in oncology and are administered to cancer patients in routine clinical care and in drug development trials as co-medication. Given their strong immune-suppressive activity, GCS may interfere with immune-oncology drugs. We are developing a therapeutic cancer vaccine, which is based on a liposomal formulation of tumor-antigen encoding RNA (RNA-LPX) and induces a strong T-cell response both in mice as well as in humans. In this study, we investigated in vivo in mice and in human PBMCs the effect of the commonly used long-acting GCS Dexamethasone (Dexa) on the efficacy of this vaccine format, with a particular focus on antigen-specif…